1988 - 2003
Reliable information on the rate of progression of cognitive
impairment was obtained in a well-characterized group of
patients with AD who were followed using standardized CERAD
assessments. Rate of decline was slower for patients with
less severe dementia. Significant weight loss was found to
be more frequent in patients than in controls. CERAD studies
also reported the impact of depression on AD, those with
early- vs. late-onset dementia, and comparisons of patients
with AD and those with schizophrenia.
Clark CM, Sheppard L, Fillenbaum GG, et al. Variability
in annual Mini-Mental State score in patients with probable
Alzheimer's disease: a clinical perspective of data from
CERAD. Arch Neurol 1999;56:857-962.
Davidson MD, Harvey P, Welsh KA, et al. Cognitive functioning
in late-life schizophrenia: a comparison of elderly schizophrenic
patients and patients with Alzheimer's disease. Am J Psychiatry
Fillenbaum GG, Beekly D, Edland SD, et al. Consortium to
Establish a Registry for Alzheimer's Disease (CERAD): Development,
data base structure, and selected findings. Top Health Inform
Galasko D, Edland SD, Morris JC, et al. CERAD Part XI. Clinical
milestones In patients with Alzeimer's disease followed over
three years. Neurology 1995;45:1451-1455.
Heyman A, Fillenbaum G, Mirra SS. CERAD: Clinical, neuropsychological,
and neuropathological components. Aging: Clin Exp Res 1991;2:416-424.
Heyman A, Fillenbaum G, Nash F, eds. Consortium to Establish
a Registry for Alzheimer's Disease: The CERAD experience.
Neurology 1997;49 (suppl 3, whole issue).
Koss E, Edland S, Fillenbaum G, et al. Clinical and neuropsychological
differences between patients with earlier and later onset
of Alzheimer's disease: a CERAD analysis, Part XII. Neurology
Koss E, Peterson B, Fillenbaum GG. Determinants of attrition
in a natural history study of Alzheimer disease. Alzheimer
Dis Assoc Disord 1999;13:209-215.
McDaniel K, Edland S, Heyman A, et al. Relationship between
level of insight and severity of dementia in Alzheimer's
disease. Alzheimer Dis Assoc Disord 1995;9:101-104.
Morris JC, Mohs RC, Rogers H, et al. CERAD: clinical and
neuropsychological assessment of Alzheimer's disease. Psychopharmacol
Morris JC, Heyman A, Mohs RC, et al. The Consortium to
Establish a Registry for Alzheimer’s Disease (CERAD)
Part I. Clinical and neuropsychological assessment of Alzheimer's
disease. Neurology 1989;39:1159-1165.
Morris JC, Edland S, Clark CM, et al. Consortium to Establish
a Registry for Alzheimer’s Disease (CERAD) Part
IV. Rates of cognitive change, a longitudinal assessment
Alzheimer's disease. Neurology 1993;43:2457-2465.
Morris JC. Clinical and neuropathological findings from
CERAD. In: Becker R, Giacobini E, eds. Alzheimer disease:
from molecular biology to therapy. Birkhauser, Boston 1997:8-12.
Weiner M, Edland S, Luszczynska H. Prevalence and incidence
of major depression in Alzheimer's disease. Am J Psychiatry
White H, Pieper C, Schmader K, et al. Weight change in Alzheimer's
disease. J Am Geriatr Soc 1996;44:265-272.
White H, Pieper C, Schmader K, et al. A longitudinal analysis
of weight change in Alzheimer's disease [letter]. J Am Geriatr
The Neuropsychology Battery developed by CERAD includes tests
of verbal fluency (naming animals); a modified 15-item
Boston Naming Test; Mini-Mental State Examination; word
list memory, recall, and recognition; constructional praxis;
and recall of constructional praxis. Word list recall was
found to distinguish best between AD patients and normal
Fillenbaum G, Wilkinson W, Welsh K, et al. Discrimination
between stages of Alzheimer's disease with subsets of Mini-Mental
State Examination items: an analysis of CERAD data. Arch
Henderson VW, Buckwalter JG. Cognitive deficits of men and
women with Alzheimer's disease. Neurology 1994;44:90-96.
Welsh K, Butters N, Hughes JP, et al. Detection of abnormal
memory decline in mild cases of Alzheimer's disease using
CERAD neuropsychological measures. Arch Neurol 1991;48:278-281.
Welsh K, Butters N, Hughes JP, et al. Detection and staging
of dementia in Alzheimer's disease - use of the neuropsychological
measures developed for CERAD. Arch Neurol 1992;49:448-452.
Welsh K, Butters N, Mohs RC, et al. CERAD Part V: a normative
study of the neuropsychological battery. Neurology 1994;44:609-614.
Fillenbaum GG, Unverzagt FW, Ganguli M, Welsh-Bohmer KA,
Heyman A. The CERAD neuropsychological battery: performance
of representative community and tertiary care samples of
African American and European American elderly. In Ferraro
FR (ed.) Minority and cross cultural aspects of neuropsychological
assessment. Swets and Zeitlinger, Lisse, NL, 2002.
Although the CERAD attempt to standardize neuroimaging measures
of AD suggests that uniform reading of brain scans at any
one clinical site was possible, uniform reading across
multiple sites proved difficult to achieve.
Davis PC, Gray L, Albert M, et al. CERAD Part III: reliability
of a standardized MRI evaluation of Alzheimer's disease.
Davis PC, Gearing M, Gray L, et al. The CERAD experience,
Part VIII: neuroimaging-neuropathology correlates of temporal
lobe changes in Alzheimer's disease. Neurology 1995;45:178-179.
Findings obtained using the CERAD neuropathology protocol
confirmed the clinical diagnosis of AD in 87% of autopsied
CERAD patients. This widely-used protocol has since been
modified for use by general pathologists for the diagnosis
of dementia. (See also section on Associated Dementias.)
Cochran EJ, Gostanian OM, Mirra SS. Autopsy practices at
CERAD and Alzheimer disease center sites: a survey of neuropathologists.
Alzheimer Dis Assoc Disord 1995;9:203-207.
Ellis RJ, Olichney JM, Thal LJ, et al. Cerebral amyloid
angiopathy in the brains of patients with Alzheimer's disease:
the CERAD experience, Part XV. Neurology 1996;46:1592-1596.
Fillenbaum GG, Huber MS, Beekly D, et al. CERAD Part XIII.
Obtaining autopsy in Alzheimer's disease. Neurology 1996;46:142-145.
Gearing M, Mirra SS, Hedreen J, et al. CERAD Part X. Neuropathology
confirmation of the clinical diagnosis of Alzheimer's disease.
Mirra SS, Heyman A, McKeel DW, et al. CERAD Part II. Standardization
of the neuropathological assessment of Alzheimer's disease.
Mirra SS, Hart MN, Terry RD. Making the diagnosis of Alzheimer's
disease: a primer for practicing pathologists. Arch Pathol
Lab Med 1993;117:132-144.
Mirra SS. Neuropathological assessment of Alzheimer's disease:
the experiences of the Consortium to Establish a Registry
for Alzheimer's Disease (CERAD). Internat Psychogeriatrics
Mirra SS, Gearing M, Sumi SM, et al. The neuropathology
assessment of Alzheimer's disease and related dementias:
the CERAD experience. In Corain B, et al., eds. Alzheimer's
disease: advances in clinical and basic research. John
Wiley & Sons
Mirra SS, Gearing M, McKeel DW, et al. Interlaboratory comparison
of neuropathology assessments in Alzheimer's disease: a CERAD
study. J Neuropath Exp Neurol 1994;53(3):303-315.
Mirra SS. The CERAD neuropathology protocol and consensus
recommendations for the postmortem diagnosis of Alzheimer's
disease: a commentary. Neurobiol Aging 1997;18(suppl):S91-S94.
Olichney JM, Ellis RJ, Katzman R, et al. Types of cerebrovascular
lesions associated with severe cerebral amyloid angiopathy
in Alzheimer's disease. Ann NY Acad Sci 1997;826:493-497.
In CERAD, as in other longitudinal studies, recruitment and
retention of African American subjects often required special
measures. When age, education, and severity of disease at
entry were controlled, race was found to have only a very
mild effect on progression of dementia.
Ballard E, Nash F, Raiford K, et al. Recruitment of black
elderly for clinical research studies of dementia: the CERAD
experience. Gerontologist 1993;33:561-565.
Fillenbaum GG, Peterson B, Welsh-Bohmer KA, et al. Progression
of Alzheimer's disease in black and white patients: the CERAD
experience, Part XVI. Neurology 1998;51:154-158.
Fillenbaum GG, Heyman A, Huber MS, Ganguli M, Unverzagt
FW. Performance of elderly African American and White community
residents on the CERAD Neuropsychological Battery. JINS 2001;7:502-509.
Welsh K, Ballard E, Nash F, et al. Issues affecting minority
participation in research studies of Alzheimer's disease.
Alzheimer Dis Assoc Disord 1994;8 Suppl 4:38-48.
Welsh K, Fillenbaum GG, Wilkinson W, et al. Neuropsychological
test performance in African-American and white patients with
Alzheimer's disease. Neurology 1995;45:2207-2211.
AD is reported to be the third most expensive disease in
the US, after heart disease and cancer. There are few published
studies on Medicare-reimbursed services for patients with
an accurate diagnosis of AD. CERAD studies indicated that
the frequency and duration of hospitalization were greater
for AD subjects than for matched controls. These studies
further indicate that multiple years of Medicare-based
data are needed to identify persons with AD.
Fillenbaum G, Heyman A, Peterson B, Pieper C, Weiman AL.
Frequency and duration of hospitalization of patients with
AD based on Medicare data: CERAD XX. Neurology 2000;54:740-743.
Fillenbaum G, Heyman A, Peterson BL, Pieper CF, Weiman AL.
Use and cost of hospitalization of patients with AD by stage
and living arrangement: CERAD XXI. Neurology 2001;56:201-206.
Fillenbaum G, Heyman A, Peterson BL, Pieper CF, Weiman AL.
Use and cost of outpatient visits of AD patients: CERAD XXII.
Taylor DH, Fillenbaum GG, Ezell ME. The accuracy of Medicare
claims data in identifying Alzheimer's disease. J Clin Epidemiol
In our study comparing the families of 118 patients with
AD and their nondemented spouses, we found a significantly
greater risk for AD among families of patients than among
those of controls. There was also a greater risk of AD
among female relatives than among males.
Edland SD, Silverman JM, Peskind ER, et al. Increased risk
of dementia in mothers of Alzheimer's disease cases: evidence
for maternal inheritance. Neurology 1996;47:254-256.
Silverman J, Raiford K, Edland S, et al. CERAD Part VI:
family history assessment: a multi-center study of relatives
of AD probands and non-demented spouse controls. Neurology
Age, sex, and severity of dementia were found to be the major
predictors of survival of patients with AD, whereas race,
education, and marital status were not important predictors.
The major predictors of time to nursing home admission
were sex, age, marital status (men only), and severity
of dementia. Death certificates were found to be poor sources
of information regarding the presence of dementia, since
dementia was not mentioned in nearly a third of the death
certificates of CERAD patients who had an overt clinical
diagnosis of AD.
Heyman A, Peterson B, Fillenbaum G, et al. CERAD Part XIV:
demographic and clinical predictors of survival in patients
with Alzheimer's disease. Neurology 1996;46:656-660.
Heyman A, Peterson B, Fillenbaum G, et al. Predictors of
time to institutionalization of patients with Alzheimer's
disease. The CERAD experience, Part XVII. Neurology 1997;48:1304-1309.
Raiford K, Anton-Johnson S, Haycox Z, et al. CERAD Part
VII: accuracy of reporting dementia on death certificates
of patients with Alzheimer's disease. Neurology 1994;44:2208-2209.
Neuropathologic examination of the brains of CERAD cases
with autopsy-confirmed AD disclosed coexisting lesions
of Parkinson’s disease in 21% of them, and of cerebrovascular
disease in an additional 28%. Patients with cerebrovascular
lesions tended to be older, more severely demented, and
performed more poorly on neuropsychology testing.
Clark CM, Ewbank D, Lerner A, et al. The relationship between
extrapyramidal signs and cognitive performance in patients
with Alzheimer's disease enrolled in the CERAD study. Neurology
Heyman A, Fillenbaum GG, Welsh-Bohmer KA, et al. Cerebral
infarcts in patients with autopsy-proven Alzheimer's disease.
CERAD. Part XVIII. Neurology 1998;51:159-162.
Heyman A, Fillenbaum GG, Gearing M, et al. Comparison of
Lewy body variant of Alzheimer's disease with pure Alzheimer's
disease: CERAD Part XIX. Neurology 1999;52:1839-1844.
Hulette C, Mirra SS, Wilkinson W, et al. CERAD Part IX:
a prospective cliniconeuropathologic study of Parkinson's
features in Alzheimer's disease. Neurology 1995;45:1991-1995.
Hulette C, Nochlin D, McKeel D, et al. Clinical-neuropathologic
findings in multi-infarct dementia: a report of six autopsied
cases. Neurology 1997;48:668-672.
Welsh-Bohmer KA, Gearing M, Saunders AM, et al. Apolipoprotein
E genotypes in a neuropathological series from CERAD. Ann
The CERAD Behavior Rating Scale for Dementia (BRSD) identified
eight behavioral domains that may be related to AD, including
agitation, depression, and hallucinatory phenomena. Both
a full (46 item) and a short (17 item) version of this
scale are available.
Patterson MB, Mack JL, Mackell JA, et al. A longitudinal
study of behavioral pathology across five levels of dementia
severity in Alzheimer's disease: the CERAD Behavior Rating
Scale for Dementia. Alzheimer Dis Assoc Disorder 1997;11:S40-S44.
Patterson MB, Mack JL. CERAD Behavioral Rating Scale for
Dementia (BRSD). Alzheimer Dis Assoc Disord 1997;11:S40-S44.
Tariot PN, Mack JL, Patterson MB, et al. The CERAD Behavior
Rating Scale for Dementia. Am J Psychiatry 1995;152:1349-1357.
Tariot PN. CERAD Behavior Rating Scale for Dementia. Int
Psychogeriatr 1996;8(suppl 3):317-320.
Mack JL, Patterson MB, Tariot PN. Behavior Rating Scale
for Dementia: Development of test scales and presentation
of data for 555 individuals with disease. J Geriatr Psychiatry
Studies In Foreign Languages
Considerable attention has been given to equivalence in translating
CERAD assessment instruments into foreign languages. Such
translations are currently being used in German-speaking
populations in Switzerland, Austria, and Germany, and in
a standardized national population study in Finland. The
following studies showed the French- and English-language
versions to be comparable.
Demers P, Robillard A, Lafleche G, et al. Translation of
clinical and neuropsychological instruments into French:
the CERAD experience. Age Ageing 1994;23:449-451.
Panisset M, Simonetto I, Boller F, et al. Performance of
normal elderly subjects using the [English and French versions
of the] CERAD neuropsychology battery. In: Poncet M, Michel
B, Nieoullon A, eds. Update on AD and related syndromes.
Marseille, Solal: 1994:357-359.
Statistics and Data Management
CERAD has developed improved methods for analyzing longitudinal
data, which maximize the amount of information provided
by a sample with rolling enrollment and different lengths
of time in the study. Less conventional approaches to examining
data, based on fuzzy set theory, have also been examined.
Edland SD, Grosser S, Barnhart R, et al. Improved efficiency
in the relationship between level and slope. American Statistical
Association. 1995 Proceedings of the Biometrics Section:
Fillenbaum GG, Woodbury M. Typology of Alzheimer's Disease:
findings from CERAD data. Aging Mental Health 1998;2:105-127.
Unger J, van Belle G, Heyman A. Cross-sectional vs. longitudinal
estimates of cognitive change in the non-demented elderly.
J Am Geriatr Soc 1999;47:559-563.
Woodbury MA, Fillenbaum GG. Psychometric characteristics
of the Mini-Mental State Examination in patients with Alzheimer's
disease: a grade of membership analysis of CERAD data: Part
II. Int J Geriatr Psychiat 1996;11:543-553.
Characteristics of the measures used and of the study population
can influence findings. We found that the widely-used Clinical
Dementia Rating Scale is indeed valid. While the most ill
patients are more likely to drop out of longitudinal studies
of nondemented elderly, studies of persons with AD showed
that the most ill are more likely to stay. Continued participation
of control subjects who are spouses of enrolled patients
is interdependent. Not surprisingly, the continued participation
of one is related to the continued participation of the
Fillenbaum GG, Peterson B, Morris JC. Estimating the validity
of the Clinical Dementia Rating scale: the CERAD experience.
Aging: Clin Exp Res 1996;8:379-385.
Peterson B. Re: Association of education with reported age
of onset and severity of Alzheimer's disease at presentation:
Implications for the use of clinical samples [letter]. Am
J Epidemiol 1996;143:1177.
Smith DS, Fillenbaum G. Comparison of spouse and community
controls within CERAD. Aging: Clin Exp Res 1994;6:151-157.
Theses and Dissertations
Barnett M. (1992) Standardization of Clinical Dementia Rating
(CDR) among 23 Alzheimer's disease study centers. Master's
thesis, Department of Biostatistics, University of Washington.
Blazina LB. (1996) Investigation of possible behavioral
profiles in Alzheimer's disease. Doctoral dissertation, The
Fielding Institute, Santa Barbara, California.
Fisher NJ. (1997) External validation of distinct neuropsychological
subgroups of Alzheimer's disease patients: preliminary findings
from the CERAD data. Doctoral dissertation, University of
Miller S. (1996) Time to nursing home admission for patients
with Alzheimer's disease: The effect of healthcare system
characteristics. Doctoral dissertation, University of Illinois.
Unger J. (1993) A comparison of longitudinal and cross-sectional
rates of decline in MMSE scores in Alzheimer's controls.
Master's thesis, Department of Biostatistics, University
Yang M. (1993) Cross-cultural comparison of the Mini-Mental
State Examination (MMSE) in patients with Alzheimer's disease.
Master's thesis, Department of Biostatistics, University
The authors of most of the following papers were not members
of the original CERAD group. They have, however, published
important studies based on CERAD data and concepts.
Ferris SH, Mackell JA. Behavioral outcomes in clinical trials
for Alzheimer disease. Alzheimer Dis Assoc Disord 1997;11
Perrault A, Oremus M, Demers L, et al. Review of outcome
measurement instruments in Alzheimer’s disease
drug trials: psychometric properties of behavior and
J Geriatr Psychiat and Neurology 2000;13:181-196.
Henderson VW, Buckwalter JG. Cognitive deficits of men and
women with Alzheimer's disease. Neurology 1994; 44:90-96.
Neumann PJ, Araki SS, Arcelus A, et al. Measuring Alzheimer's
disease progression with transition probabilities: estimates
from CERAD. Neurology 2001;57:951-964.
Olichney JM, Galasko D, Salmon DP. Cognitive decline is
faster in Lewy body variant than in Alzheimer's disease.
Miller SC, Prohaska TR, Furner SE, et al. Time to nursing
home admission for persons with Alzheimer's disease: the
effect of health care system characteristics. J Gerontol:
Social Sciences 1998;53B:S341-S353.
Ganguli M, Ratcliff G, Huff FJ. Effects of age, gender,
and education on cognitive tests in a rural elderly
sample. Neuroepidemiology 1991;10:42-52.
Guruje O, Unverzagt FW, Osuntokun BO. The CERAD Neuropsychological
Test Battery: norms from a Yoruba-speaking Nigerian sample.
West African J Med 1995;14:29-33.
Lee DY, Lee JH, Ju YS, et al. The prevalence of dementia
in older people in an urban population of Korea: the Seoul
study. J Am Geriatr Soc 2002;50:1233-1239.
Liu CK, Lai CL, Tai CT, et al. Incidence and subtypes of
dementia in southern Taiwan: impact of socio-demographic
factors. Neurology 1998;50:1572-1579.
Riley KP, Snowdon DA, Saunders AM, et al. Cognitive function
and apolipoprotein E in very old adults: findings from
the Nun Study. J Gerontol Series B-Psychological Sciences & Social
Unverzagt FW, Hui SL, Farlow MR et al. Cognitive decline
and education in mild dementia. Neurology 1998;50:181-185.
Neuropathology Group. Medical Research Council Cognitive
Function and Aging Study. Pathological correlates of
late-onset dementia in a multicentre, community based
Lancet 2002; 359: 624-625.
Stewart R, Richards M, Brayne C. Cognitive function in UK
community-dwelling African Caribbean elders: normative
data for a test battery. Int J Geriatr Psych 2001; 16:518-527.
Gillen TE, Gregg KM, Yuan H, et al. Clinical trials in
disease. Calculating Alzheimer Disease Assessment Scale -
cognitive subsection with the data from the Consortium to
Establish a Registry for Alzheimer’s Disease. Psychopharm
Mendiondo MS, Ashford JW, Kryscio RJ. Modeling mini-mental
state examination changes in Alzheimer's disease. Stat Med
Lee JH, Lee KU, Lee DY, et al. Development of the Korean
version of the Consortium to Establish a Registry for
disease. J Gerontol Series B-Psychological Sciences & Social
Berres M, Monsch AU, Bernasconi F, et al. Normal ranges
of neuropsychological tests for the diagnosis of Alzheimer's
disease. Studies In Health Technology and Informatics 2000;77:195-199.
version of this page.